In vivo assessment of dual-function submicron textured nitric oxide releasing catheters in a 7-day rabbit model

• Published in: Acta biomaterialia Vol. 180; pp. 372 - 382
• Main Authors: Wu, Yi, Xu, Li-Chong, Yeager, Eric, Beita, Keren Gabriela, Crutchfield, Natalie, Wilson, Sarah N., Maffe, Patrick, Schmiedt, Chad, Siedlecki, Christopher A., Handa, Hitesh
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2024
• Subjects: Animals; Catheters; Cell Line; Disease Models, Animal; Hemocompatibility; Humans; Materials Testing; Nitric oxide; Nitric Oxide - metabolism; Platelet Adhesiveness - drug effects; Rabbit model; Rabbits; S-nitroso-N-acetylpenicillamine; S-Nitroso-N-Acetylpenicillamine - chemistry; S-Nitroso-N-Acetylpenicillamine - pharmacology; Textured topography; Thrombosis - pathology; S-nitroso-N-acetylpenicillamine; Rabbit model; Textured topography; Nitric oxide; Hemocompatibility
• ISSN: 1742-7061; 1878-7568; 1878-7568
• DOI: 10.1016/j.actbio.2024.04.009

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dualfunction submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response. [Display omitted]